Cancer Treatment

Cyclosporin for ITP

There are patients with refractory autoimmune thrombocytopenia do not respond to standard therapy with high-dose corticosteroids, WinRHO, Rituxan, IVGG, and splenectomy. Cyclosporin is useful for some patients who occasionally respond to it. There are many published case reports of its effectiveness. It is recommended for refractory cases in standard reviews.

Since very few pateints are this refractory, prospective studies are not possible but cyclosporine is widely accepted, including being mentioned in compenida for off-label use for Evan's syndrome which is a combination of immune thrombocytopenia and hemolytic anemia.

D B. Cines and J. B. Bussel
How I treat idiopathic thrombocytopenic purpura (ITP)
Blood, October 1, 2005; 106(7): 2244 - 2251.

Kappers-Klunne MC, van't Veer MB. Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenia purpura refractory to corticosteroids or splenectomy. Br J Haematol. 2001;114: 121-125

Bourgeois E, Caulier MT, Delarozee C, et al. Long-term follow-up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis. Br J Haematol. 2003;120:1079-1088

WinRho for Immune Thrombocytopenic Purpura (ITP)

Immune (or idiopathic) thrombocytopenic purpura (ITP) is commonly encountered by the practicing hematologist. Clinical management decisions have traditionally been guided by individual training and past experience. Input from the literature has been more from observational reports of case series than from scientific results of hypothesis-driven research. Practice guidelines and several surveys of clinical hematology practice have highlighted important questions in the field, and in the past 5 to 10 years both clinical and laboratory investigations have produced valuable new information, especially about options in refractory disease. Unfortunately, the last comprehensive guideline  have been published a decade ago.

Generally, the standard of practice for patients who cannot maintain an adequate platelet count on tapering steroids is to undergo splenectomy. In 60% to 70% of patients this restores a normal platelet count for at least 5 to 10 years. It allows those patients who respond to this procedure to avoid both the risks of low platelet counts and the toxicity of daily steroids. However, although both the site of platelet destruction and the response to intravenous immunoglobulin (IVIG) have been suggested to predict response to splenectomy, there is no universally acknowledged way to predict which patients will respond. SOme patients do not respond and otehrs relapse, sometimes due to a regrowth of accessory spleen tissue. WHen clearly identifeid, an accessory spleen should be removed, if spenectomy reviously resulted in a remission. However, the decision  to repeat what is now an open splenectomy is fraught with uncertainty. Patients are often reluctant to be exposed to the inherent risks of surgery and the small but significant risk of overwhelming sepsis after splenectomy without a guarantee of success. It is acceptable to proceed with other therapies at that point. Anti-RhD is one such option.

IV anti-D is a safe and effective treatment in approximately two thirds of Rh+, nonsplenectomized adults with ITP and can be used as a steroid-sparing agent. There is no reason to believe that anti-D is curative or that it affected the natural history of the ITP in these adults. Rather, it appeared to give patients time to improve on their own.

George JN, Woolf SH, Raskob GE, et al. Idiopathic Thrombocytopenic Purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3–40.

Cines DB, Bussel JB. How I treat idiopathic thrombocytopenic purpura (ITP). Blood. 2004;106:2244–2251.

Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346:995–1008

Cooper N, Woloski BMR, Fodero EM, Novoa M, Leber M, Bussel JB. Does treatment with intermittent infusions of IV anti-D allow a proportion of adults with recently diagnosed immune thrombocytopenic purpura (ITP) to avoid splenectomy? Blood. 2002;99: 1922

Rituximab for ITP

The state of the field regarding Rituxan in ITP until recently has been sceptical because only case reports and case series have been reported. Publication bias leads to under-reporting of negative results and over-reporting of positive results. In three large cohorts of adults who had failed multiple therapeutic modalities, patients were treated with the regimen of anti-CD20 used to treat B-cell lymphoma—375 mg/m2 weekly for 4 weeks. Approximately 50% of patients had a partial or complete response, and about 33% had durable remissions. However more recently a prospective study in the pediatric population rvealed a 31% response rate. Rituximab for other than first line has been recommended in a recent treatment review in a major journal and is being increasingly used.Medicare lists it as reimbursable.

Since the last review I became aware of an additional recent critical review. It states: "While these studies clearly document the therapeutic efficacy of rituximab in chronic, refractory ITP in both adults and children, we still do not know which ITP patients should receive rituximab therapy. In contrast to CAD, in which the relatively efficient treatment with rituximab can be compared to several ineffective conventional therapies even in the absence of comparative phase 3 studies, further trials are definitively needed in order to determine the place of rituximab in the treatment of ITP."

Stas et al, Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura Blood, 15 August 2001, Vol. 98, No. 4, pp. 952-957

Idiopathic Thrombocytopenic Purpura (ITP) and Anti-CD20 Monoclonal Antibody: A Case Report.
Clinical and Applied Thrombosis/Hemostasis, October 1, 2006; 12(4): 489 - 492

S. Berentsen
Rituximab for the treatment of autoimmune cytopenias
Haematologica, December 1, 2007; 92(12): 1589 - 1596.

M. Ruggeri, S. Fortuna, and F. Rodeghiero
Heterogeneity of terminology and clinical definitions in adult idiopathic thrombocytopenic purpura: a critical appraisal from a systematic review of the literature
Haematologica, January 1, 2008; 93(1): 98 - 103.
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C. M. Bennett, Z. R. Rogers, D. D. Kinnamon, J. B. Bussel, D. H. Mahoney, T. C. Abshire, H. Sawaf, T. B. Moore, M. L. Loh, B. E. Glader, M. C. McCarthy, B. U. Mueller, T. A. Olson, A. N. Lorenzana, W. C. Mentzer, G. R. Buchanan, H. A. Feldman, E. J. Neufeld, and the Pediatric Rituximab/ITP Study Group and the Gl
Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura
Blood, April 1, 2006; 107(7): 2639 - 2642

Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001;98:952–957.

Cooper N, Stasi R, Cunningham-Rundles S, et al. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol. 2004;125:232–239.

Braendstrup P, Bjerrum OW, Nielsen OJ, et al. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura. Am J Hematol. 2005;78:275–280.

A. L. Perrotta Re-treatment of Chronic Idiopathic Thrombocytopenic Purpura With Rituximab: Literature Review Clinical and Applied Thrombosis/Hemostasis, January 1, 2006; 12(1): 97 - 100.

D. B. Cines and J. B. Bussel How I treat idiopathic thrombocytopenic purpura (ITP)
Blood, October 1, 2005; 106(7): 2244 - 2251.

Intravenous gammaglobulin for ITP

Lay Summary: IVIG is standard for ITP but represents a "holding action" rather than a cure.

IVIG is approved by the FDA for use in the treatment of the following diseases: Kawasaki disease, dermato/polymyositis, idiopathic thrombocytopenic purpura (ITP), Guillain-Barre syndrome, polyneuropathy, some viral diseases, and some forms of immune deficiency. The place of IVIG in the treatment of ITP is not well clarified. It does not modify the disease as do steroids and splenectomy, but only gains a temporary rise in platelet counts, until definitive therapy can be planned or accomplished. There are ongoing shortage that jeopardize long term therapy. In addition, a number of alternatives exist, including: Anti-RhoD, vincristine, Rituximab, danazol, high dose pulse steroids and even chemotherapy. IVIG is accordingly best used as a temporary measure, to prepare the apteint for spenectomy or while discussions of other treatments take place. It is also occasionally used to wait and see if a spontaneous remission of theITP occurrs; however, this use is less supported by the literature.
Based on the literature, CMS advises the following:IVIG is indicated for chronic ITP only when all of the following conditions are met:

Prior treatment with corticosteroids and splenectomy;
Duration of illness less than 6 months;
Age of 10 years or older;
No concurrent illness/disease explaining thrombocytopenia; and
Platelet counts persistently at or below 20,000/ml.

George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, Blanchette VS, Bussel JB, Cines DB, Kelton JG, Lichtin AE, McMillan R, Okerbloom JA, Regan DH, Warrier I: Idiopathic thrombocytopenic purpura: A practice guideline developed by explicit methods for the American Society of Hematology. Blood 88:3, 1996

Cines DB, Blanchette VS: Immune thrombocytopenic purpura. N Engl J Med 2002 Mar 28; 346(13): 995-1008

Kahn MJ, McCrae KR: Splenectomy in Immune Thrombocytopenic Purpura: Recent Controversies and Long-term Outcomes. Curr Hematol Rep 2004 Sep; 3(5): 317-23

McMillan R, Durette C: Long-term outcomes in adults with chronic ITP after splenectomy failure. Blood 2004 Aug 15; 104(4): 956-60